Reduce and impaired NK cells in the IPF lungs

What is it about?

Rationale: Idiopathic Pulmonary Fibrosis (IPF) is an age-related lung disease in which there is an accumulation of senescent cells. Senescent cells are eliminated during tissue repair, whereas with aging, the mechanisms of clearance are impaired, resulting in the accumulation of senescent cells. Objectives: To determine the proportion and activity of NK cells in the lung of IPF patients as one of the main agents involved in the accumulation of senescent cells. Methods: NK cell populations were determined in lung tissue and peripheral blood of IPF and controls. Cytotoxic and transwell assays were performed using NK cells and lung fibroblast conditioned media Measurements and main results: We observed a decrease in the population of NK cells principally in the IPF lower lobes. Single-cell RNA-seq of the IPF lung revealed differences between controls and IPF in the NK cluster, with an increased expression of activation genes in areas of low fibrosis (upper lobes) and a pro-senescent gene pattern in more fibrotic areas (lower lobes). Conclusions: We propose that defects in NK activity could be one of the mechanisms responsible for the perpetration of the accumulation of senescent cells in IPF lungs.

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Why is it important?

Impact on medicine and basic research: We have identified an impaired NK immune response in the lung of patients with IPF which may be enabling the accumulation of senescent cells through a deficient clearance. This study can open a new gate for the treatment of senescent cells in IPF.